This invention relates to apparatus for the storage of organs for transplantation and physiology in general and, more particularly, to apparatus for the storage of an organ securely held and maintained at a desired temperature during either static storage or perfusion of the organ.
As improvements in clinical transplantation of human organs advance, there is a growing need for preserving organs until they can be transplanted. Because the location of the donated organ may be a considerable distance from the transplantation location and there may be delays prior to transplantation, it is necessary to preserve the organ while transporting the organ to the place of transplant or holding the organ at the place of transplant.
Currently, organs preserved for clinical transplantation are stored either by being placed into a container and surrounded by ice or by being continuously perfused. Continuous perfusion provides superior storage of organs but is rarely employed because of the expense, hazardousness, and awkwardness of transportation as compared to the overall convenience and inexpensiveness of ice storage.
The static storage of organs in ice has a number of disadvantages that have not received adequate attention to date. For example, organs stored in conventional plastic containers may be harmed during transport by unrestrained or insufficiently restrained movements within these containers. The shapes of these containers bear no resemblance to the shapes of the organs contained therein. This may result in the collision of the organ with the walls of the container causing damage to the organ.
Some surgeons have recognized this and provide some protection against collision by placing gauze pads surrounding the organ. This practice may also damage the organ. Gauze may contain or shed particulates into the perfusate or fluid that may become emboli if introduced by chance into the artery. Additionally, gauze, by design, has a somewhat rough surface. Kidneys and hearts may be physically solid enough to resist damage from contact with this rough surface. Livers, pancreases, and lungs, however, are remarkably delicate and may be harmed by contact with gauze. The use of cloth towels may also be ineffective due to uneven organ support or insufficient space for towels in the container.
The storage of the organ in an ice chest also exposes the organ to possibly harmful vibrations. The vibrations encountered by the ice chest are transferred to the organ within the container (such as, for example, shocks from rolling a cart holding the chest over a tile floor or a sidewalk, slamming the ice chest down onto a receiving surface, rolling the cart off a sidewalk and onto a street, transporting the chest over railroad tracks or sitting on the seat of a vibrating small aircraft). These vibrations or shocks may, again, damage the organ. The same vibrations may also damage an organ subjected to standard continuous perfusion.
Recent research indicates a general tendency toward cold denaturation of many proteins at 0.degree. C. and empirical observations on the storage of organs at temperatures above 0.degree. C. indicate that the storage of organs above 0.degree. C. is superior to storage at 0.degree. C. This is applicable for static organ storage. This implies that the use of ice does not provide for organ storage at an optimum temperature. To the contrary, the storage of organs in ice may actually result in damage to the organ. It is entirely possible that the detrimental effects of long-term ice storage are due primarily to cold denaturation and/or storage at a suboptimum temperature.
A further disadvantage of the use of ice for storing organs is that ice melts. This melting limits the available storage time and also raises the need to dispose of the melted ice or to find new ice during transportation of the organ. Furthermore, it also requires that an ample supply of ice be on hand at the originating hospital.
Additionally, ice is generally not sterile. The storage of organ containers surrounded by ice raises a genuine hazard of contamination of the organ. Microbes from the melted ice that covers the lid of the storage container may contaminate the organ when it is removed from the storage container. The microbes may then be transplanted into the immunosuppressed recipient. It may be very difficult to avoid this problem.
Furthermore, the viability of an organ stored in a container in ice cannot be judged. Additionally, the storage history of the organ cannot be verified. Typically, organ temperature cannot be checked after transport to ensure the absence of any irregularities. Also, the actual, verifiable cold storage time, which may be critical for evaluating the suitability of an organ, may not be known or may not be known with sufficient accuracy.
An apparatus for perfusing organs at a reduced cost, reduced risk, and with fewer transportation difficulties and that would allow the detrimental effects of prolonged ice storage to be avoided is desirable. There have been recent attempts to provide portable perfusion apparatus for transporting organs. None of these perfusion machines protect the organ from the eventuality of damage due to uncontrolled warming if the perfusion machine should stop functioning for any reason.
U.S. Pat. No. 3,995,444 to Clark et al. discloses a portable organ perfusion system. The system provides for extracorporeal perfusion of organs wherein a pulsatile flow of cold perfusate is circulated through an organ intended for transplantation. The system includes a perfusion chamber, a heat exchanger comprising ice water bath containing a coil of tubing through which the perfusate is circulated, and a pulsatile pump interposed in the line between the heat exchanger and the perfusion chamber, downstream of that exchanger, for drawing cold perfusate through the exchanger and directing it in a series of regular pulses to the organ.
U.S. Pat. No. 4,745,759 to Bauer et al. discloses a portable machine that may be operated by a portable battery pack. The machine is capable of perfusing one or more organs in a temperature controlled environment. A thermoelectric refrigeration system regulates the temperature of the perfusate delivered to the organ. The temperature of the perfusate is automatically controlled within selectable parameters by microprocessor circuitry. An alarm system calls attention to changes in temperature, pressure, flow and voltage parameters that exceed selected conditions. The Bauer perfusion system and the perfusion systems produced by Waters Instruments of Rochester, Minnesota do not include any thermal insulation for the organ cassette.
U.S. Pat. No. 5,217,860 to Fahy et al. discloses a computer-controlled apparatus for perfusing an organ. The apparatus includes a plurality of fluid reservoirs and an organ container. One or more sensors are located within the fluid flow path for sensing the concentration, temperature, pH and pressure of the fluid flowing through the apparatus. The apparatus is contained within a refrigerated cabinet.
The present invention provides a novel approach to organ perfusion which precludes rapid organ warming when perfusion is terminated, and is designed also to function as a static storage device for organs.